We have identified a natural cytotoxin to tumor cells in 73% of normal sera. This cytotoxin exists in serum as a complex with antiglobulin which binds with and inactivates the antigen combining region of the 7s IgG cytotoxin. It is possible to displace the antiglobulin with a second IgG antiglobulin which is present in rheumatoid factor positive serum. This is accomplished by the allogeneic second antiglobulin combining with the Fab' portion of complexed cytotoxin and thereby causing conformational changes at the antigen combining region of the cytotoxin. Soluble antigen from susceptible tumor cells also inactivates the 7s cytotoxin but can be decomplexed like autologous antiglobulin by the second allogeneic antiglobulin. First we wish to seeek information on the range of tumor classes and tumors within classes to which our natural cytotoxin is cytotoxic. We also want to see if this antibody is injurious to embryonic cells that may bear oncofetal antigens and confirm that it is not injurious to normal tissues. Secondly, we wish to see if we are dealing with a single antibody or a family of antibodies by adsorbing with tumor A cells and then testing for cytotoxicity on tumor B cells. Third, through inhibition of 7s cytotoxin with increasing concentrations of KCl extracts of tumor cells and then testing for cytotoxicity, we wish to determine antigen burden on cells from different tumors. This can be compared with susceptibility of cell source of extract to injury with the cytotoxin. Finally, we wish to purify antigen from 3M KCl extracts of susceptible tumor cells and develop a radioimmunoassay for antigen(s) that react with our cytotoxin. This radioimmunoassay will then be applied to serologic studies on cord and adult blood from healthy subjects and patients with cancer.